Methods and systems for electrical and/or drug stimulation as a therapy for erectile dysfunction

ABSTRACT

Systems and methods for introducing one or more stimulating drugs and/or applying electrical stimulation to tissue affecting the penis to treat erectile dysfunction (for instance, following prostate surgery) uses at least one implantable system control unit (SCU) producing electrical pulses delivered via electrodes and/or producing drug infusion pulses, wherein the stimulating drug(s) are delivered via one or more pumps and infusion outlets.

The present application is a Continuation of U.S. Pat. No. 6,885,895, tobe issued on Apr. 26, 2005, which patent claims the benefit of U.S.Provisional Patent Application Ser. No. 60/286,744, filed Apr. 26, 2001,which patent and application are incorporated herein by reference intheir respective entireties.

FIELD OF THE INVENTION

The present invention relates to implantable drug delivery andelectrical stimulation systems and methods, and more particularlyrelates to utilizing one or more implantable devices to deliverelectrical stimulation and/or one or more stimulating drugs as a therapyfor erectile dysfunction, for instance, following prostatic surgery.

BACKGROUND OF THE INVENTION

Recent estimates suggest that the number of U.S. men with erectiledysfunction may be near 10 to 20 million, and inclusion of individualswith partial erectile dysfunction increases the estimate to about 30million. Erectile dysfunction has a number of etiologies, includingneuropathy and vascular disease. The male erectile response is initiatedby the action of neurons, or nerve cells (i.e., neuronal action), and ismaintained by a complex interplay between events involving blood vessels(i.e., vascular events) and events involving the nervous system (i.e.,neurological events).

The part of the nervous system that regulates involuntary action (e.g.,the intestines, heart, glands) is the autonomic nervous system. Theautonomic nervous system is divided into two mutually antagonistic,physiologically and anatomically distinct systems: the sympatheticnervous system and the parasympathetic nervous system. The sympatheticnervous system originates in the thoracic and lumbar regions of thespinal cord, and in general, opposes the physiological affects of theparasympathetic nervous system. For instance, the sympathetic systemtends to reduce digestive secretions or speed up the heart, usually whenan individual is in an active state. The parasympathetic nervous systemoriginates in the brain stem and the lower part of the spinal cord, and,in general, opposes the physiological effects of the sympathetic nervoussystem. Thus, the parasympathetic nervous system tends to stimulatedigestive secretions or slow the heart, usually when an individual is ina relaxed state.

It is parasympathetic neuronal action that initiates the male erectileresponse. Specifically, this parasympathetic input originates from thepelvic splanchnic nerve plexus. The pelvic splanchnic nerve plexus iscomprised of branches from the second, third, and fourth sacral nerves(from the lower part of the spinal cord) that intertwine with theinferior hypogastric plexus, which is a network of nerves in the pelvis.The cavernous nerves (designated greater and lesser) are derived fromthe pelvic splanchnic nerves, via the prostatic plexus, and supplyparasympathetic fibers to the corpora cavernosa and corpus spongiosum,the spongy tissues in the penis that are engorged with blood during anerection. The corpora cavernosa are two paired tissue bodies that liedorsally in the penis, while the corpus spongiosum is located ventrallyand surrounds the urethra. The corpus spongiosum expands at the terminalend to form the glans penis. These erectile tissues are composed ofvenous spaces lined with epithelial cells separated by connective tissueand smooth muscle cells.

Parasympathetic activity allows erection by relaxation of the smoothmuscle (i.e., muscle found in the walls of internal organs, bloodvessels, hair follicles, etc. that contracts without voluntary control)and dilation of the helicine arteries, which are arteries found in theerectile tissue of the penis. The dilation of the arteries causesgreatly increased blood flow through the erectile tissue, which leads toexpansion of the corpora cavernosa and the corpus spongiosum. As thecorpora cavernosa and the corpus spongiosum expand, the venousstructures draining the penis are compressed against the fasciasurrounding each of the erectile tissues (i.e., the tunica albuginea ofthe corpora cavernosa and the tunica albuginea of the corpusspongiosum). Thus, the outflow of blood is restricted, and the internalpressure increases. This vein-obstruction process is referred to as thecorporal veno-occlusive mechanism.

Conversely, sympathetic innervation from the hypogastric nerves and/orcertain nerves of the inferior hypogastric plexus, which derive from thesympathetic ganglia, inhibit parasympathetic activity and causeconstriction of the smooth muscle and helicine arteries, making thepenis flaccid. The flaccid state is maintained by continuous sympathetic(alpha-adrenergic) nervous system stimulation of the penile bloodvessels and smooth muscle.

Erectile dysfunction has a number of causes, both physiological andpsychological, and in many patients the disorder may be multifactorial.The causes include several that are essentially neurologic in origin.Damage to the spinal cord may produce varying degrees of erectilefailure depending on the location and severity of the damage. Damage tothe pathways used by the autonomic nervous system to innervate the penismay interrupt “psychogenic” erection initiated by the central nervoussystem. Damage to somatic nervous pathways may impair reflexogenicerections and may interrupt tactile sensation needed to maintainpsychogenic erections. Not only do traumatic lesions affect erectileability, but disorders leading to peripheral neuropathy may impairneuronal innervation of the penis or of the sensory afferents. Theendocrine system itself, particularly the production of androgens,appears to play a role in regulating sexual interest, and may also playa role in erectile function.

Erectile dysfunction is a common complication of prostate surgery, suchas prostatectomy (surgical removal of all or part of the prostate),which is a mainstay of treatment for prostate cancer. Approximately180,000 new cases of prostate cancer will occur in the US each year,with 35,000 men expected to die of the disease annually. A January 2000study of 1,042 men diagnosed with primary prostate cancer and whounderwent radical prostatectomy for localized prostate cancer showedthat at least 18 months following surgery, 59.9 percent were impotentand 8.4 percent were incontinent. At 24 months, 59.9 percent of menreported that erections were not firm enough for sexual intercourse, and44.2 percent were unable to have any erections.

Among men who were not impotent before surgery, the proportion of menwho reported being impotent 18 or more months after surgery variedaccording to whether a nerve-sparing procedure was attempted.Nerve-sparing procedures attempt to leave intact one or both of the“neurovascular bundles” which pass close to the prostate capsule. Inmost cases, the “bundles” are essential for achieving and maintaining anerection. In the January 2000 study, 65.6 percent of non-nerve-sparing,58.6 percent of unilateral nerve-sparing, and 56.0 percent of bilateralnerve-sparing procedures produced impotence. Despite the level ofurinary incontinence and sexual dysfunction reported in this study, mostmen (71.5 percent) reported they would choose radical prostatectomyagain.

To achieve improved outcomes in nerve-sparing surgery, devices areavailable for intra-operative cavernous nerve stimulation, often withpenile tumescence monitoring. The UroMed CAVERMAP® Surgical Aid is anexample of such a device. The CAVERMAP® Surgical Aid is an acuteneurostimulator used to stimulate the cavernous nerves during prostatesurgery. Upon such stimulation, the penis becomes erect within 20seconds to 1 minute. During a typical procedure, the CAVERMAP® SurgicalAid is used initially to establish the baseline erectile response tostimulation via stimulation bilaterally at the posterolateral urethra.As the surgery progresses and the neurovascular bundle is visualized,the CAVERMAP® Surgical Aid is used to stimulate bilaterally along thelateral pedicles at the apex, mid, and base of prostate. Part or all ofthe prostate and seminal vesicles are removed, sparing those portionscontaining the cavernous nerves.

There are few good options for men suffering from erectile dysfunctionfollowing prostatic surgery. A well-publicized oral medication,sildenafil citrate (available from Pfizer Inc. of New York, N.Y.) underthe trademarked name VIAGRA®, is available, but requires an hour toexert its full effects, and may have significant side effects such asabnormal vision, flushing, headache, and diarrhea. Vardenafil is amedication undergoing clinical investigation, which has a mechanism ofaction similar to sildenafil. Despite its drawbacks, the ability topreserve erectile function following prostate surgery has been favorablyaffected by the availability of sildenafil. Sildenafil appears to bemost effective when there is some remaining erectile function.

Intracavernosal injection therapy, in which a patient injectsvasodilator substances (e.g., alprostadil, papaverine, phentolamine)into the corpora of the penis, suffers a high rate of patient dropout.The most commonly used drug is alprostadil. Alprostadil is naturallyoccurring prostaglandin E₁, or PGE₁, that is present in the penis and isinvolved in the natural erection process. (Thus, “alprostadil”,“prostaglandin E₁”, and “PGE₁” are used interchangeable herein.)Alprostadil has been used in the treatment of impotence in the UK since1994. Alprostadil relaxes the blood vessels and muscles in the erectiletissue of the penis allowing increased blood flow, the basis of a normalerection.

Intracavernosal injection therapy suffers a high rate of patientdropout, as does the therapeutic application of vacuum constrictiondevices. Several forms of penile prostheses are available, includingsemirigid, malleable, and inflatable, but these have significantproblems with mechanical failure, infection, and device erosion. As hasbeen shown, various stimulation devices and medications have beenproposed for treating erectile dysfunction, most with significantdrawbacks.

SUMMARY OF THE INVENTION

The invention disclosed and claimed herein provides, inter alia, meansfor implanting electrode(s) and/or catheters during prostate surgery. Ifstimulation is not needed to aid erectile function, thelead(s)/catheter(s) may be removed or may alternatively remain in thebody. If the patient experiences erectile dysfunction, however, thelead(s)/catheter(s) are used to stimulate certain structures, such asthe cavernous nerves, to determine the efficacy of electrical and/ordrug stimulation. In patients who respond favorably, chronic stimulationmeans may then be implanted.

Systems and methods of the present invention provide the application ofa stimulating drug(s) alone or in combination with electricalstimulation. Drug stimulation of specific sites innervating and/orwithin the penis and surrounding areas may have significant therapeuticbenefit in restoring the patient's erectile function. For instance,infusing substances into the penis and/or its arterial supply mayprovide effective therapy. Additional uses of the present inventioninclude application to emission (discharge of semen) and ejaculation(ejection of semen in orgasm).

The invention is carried out via one or more system control units (SCUs)that apply electrical stimulation and/or one or more stimulating drugsto one or more predetermined stimulation sites. In some forms of SCUs,one or more electrodes are surgically implanted to provide electricalstimulation from an implantable signal/pulse generator (IPG) and/or oneor more infusion outlets and/or catheters are surgically implanted toinfuse drug(s) from an implantable pump. When necessary and/or desired,an SCU provides both electrical stimulation and one or more stimulatingdrugs. Some forms of the disclosed systems also include one or moresensors for sensing symptoms or other conditions that may indicate aneeded treatment.

The SCU used with the present invention possesses one or more of thefollowing properties, among other properties:

-   -   at least two electrodes for applying stimulating current to        surrounding tissue and/or a pump and at least one outlet for        delivering a drug or drugs to surrounding tissue;    -   electronic and/or mechanical components encapsulated in a        hermetic package made from biocompatible material(s);    -   an electrical coil or other means of receiving energy and/or        information inside the package, which receives power and/or data        by, for instance, inductive or radio-frequency (RF) coupling to        a transmitting coil placed outside the body, thus avoiding the        need for electrical leads to connect devices to a central        implanted or external controller;    -   means for receiving and/or transmitting signals via telemetry;    -   means for receiving and/or storing electrical power within the        SCU; and    -   a form factor making the SCU implantable in a target area in the        body.

An SCU may operate independently, or in a coordinated manner with otherimplanted SCUs, other implanted devices, or with devices external to thepatient's body. For instance, an SCU may incorporate means of sensingerectile dysfunction, which information may be used to control theelectrical and/or drug stimulation parameters in a closed loop manner.The sensing and stimulating means may be incorporated into a single SCU,or a sensing means may communicate sensed information to at least oneSCU with stimulating means.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

The above and other aspects of the present invention will be moreapparent from the following more particular description thereof,presented in conjunction with the following drawings wherein:

FIG. 1A depicts the nerves of the male pelvic viscera and surroundinganatomy, where a stimulation system of the present invention may beimplanted;

FIG. 1B illustrates the innervation of the male reproductive organs;

FIG. 2 is a section view through the body of a penis;

FIG. 3 is left paramedian section view showing the arteries and veins ofthe male pelvis;

FIGS. 4A, 4B, and 4C show some possible configurations of an implantablemicrostimulator of the present invention;

FIG. 5 depicts internal and external components of certain embodimentsof the invention;

FIG. 6 illustrates internal and external components of variousembodiments of the invention; and

FIG. 7 depicts a system of implantable devices that communicate witheach other and/or with external control/programming devices.

Corresponding reference characters indicate corresponding componentsthroughout the several views of the drawings.

DETAILED DESCRIPTION OF THE INVENTION

The following description is of the best mode presently contemplated forcarrying out the invention. This description is not to be taken in alimiting sense, but is made merely for the purpose of describing thegeneral principles of the invention. The scope of the invention shouldbe determined with reference to the claims.

FIG. 1A depicts the nerves of a male pelvis, and FIG. 1B is a schematicrepresentation of the sympathetic and parasympathetic fibers of theautonomic nervous system that are responsible for innervation of themale reproductive organs. The parasympathetic input that initiates themale erectile response originates in the pelvic splanchnic nerve plexus.The pelvic splanchnic nerves 100 are comprised of parasympatheticbranches from the second, third, and fourth sacral nerves (S2, S3, S4,respectively) that intertwine with the inferior hypogastric plexus 104.Greater cavernous nerve 108 and lesser cavernous nerve 112 are derivedfrom the pelvic splanchnic nerves 100, via the prostatic plexus 107, andcarry the parasympathetic input to the corpora cavernosum 116 and corpusspongiosum 128. Sympathetic input from the inferior hypogastric plexus104 and its branches, which derive from the hypogastric nerves 178 andthe sympathetic ganglia, inhibit erection.

Referring next to FIG. 2, the parasympathetic signals carried to thecorpora cavernosum 116 and corpus spongiosum 128 cause relaxation ofsmooth muscle surrounding the arteries and arterioles of the penis anddilation of the arteries and arterioles of the penis. The dilation ofthe arteries and arterioles causes increased blood flow through theerectile tissue, which leads to expansion of the corpora cavernosa 116and the corpus spongiosum 128. Due to this expansion, the venousstructures draining the penis are compressed against the corporacavernosum's tunica albuginea 136 and the corpus spongiosum's tunicaalbuginea 138. Thus, the outflow of blood is restricted, and theinternal pressure increases.

The arteries bringing blood to the cavernous spaces of the penis are thedeep arteries of the penis 140 and branches from the dorsal arteries ofthe penis 142. Referring now to FIG. 3, the internal iliac artery 144,after giving off a superior gluteal artery 145 and an inferior glutealartery 147, forms the internal pudendal artery 148. The internalpudendal artery 148 branches into the deep arteries of the penis 140 andthe dorsal arteries of the penis 142. The dorsal arteries 142 supplyblood to the erectile tissue of the glans penis. The deep arteries 140supply the two corpora cavernosa 116. Some of these arteries assume atendril-like appearance, forming convoluted and somewhat dilated vesselsreferred to as helicine arteries. The helicine arteries end in smallcapillary branches supplying the cavernous spaces, and are most abundantin the back part of the corpora cavernosa 116.

The blood from the cavernous spaces is returned by a series of vessels,some of which emerge in considerable numbers from the base of the glanspenis and converge on the dorsum of the organ to form the deep dorsalvein 150; others travel along the upper surface of the corpora cavernosato join the deep dorsal vein 150; some emerge from the under surface ofthe corpora cavernosa and wind around the sides of the corpora cavernosato end in the deep dorsal vein 150; and a number of veins travelseparate from the deep dorsal vein 150 and exit at the base of thepenis.

The events that promote erection begin with sexual stimulation, whichtriggers the parasympathetic nervous system to releaseneurotransmitters. In the penis, the cavernous nerves releaseneurotransmitters into the endothelial cells of the arteries.Acetylcholine is the neurotransmitter believed to be responsible fortriggering the chain of events that leads to a penile erection.Acetylcholine binds to the endothelial cells and causes the synthesisand release of nitric oxide (NO). NO is released from endothelial cellsnear the corpus cavernosum and diffuses to the smooth muscle cells,where it binds to its target, an enzyme, guanylyl cyclase. Binding of NOto guanylyl cyclase causes a conformational change in the enzyme thatleads to an increase in the production of the second messenger guanosine3′,5′-cyclic monophosphate (a.k.a. cyclic GMP or cGMP) from guanosinetriphosphate (GTP). The rate of production of cGMP in smooth musclecells has been observed to increase by at least 400 times due to theinteraction of guanylyl cyclase and NO. The increased production of cGMPresults in the amplification of the action of cGMP on smooth muscle.

Smooth muscle relaxation in the corpus cavernosum is induced by cGMP,but the way in which it does this is not exactly known. Despite the lackof clarity on the mechanism, it is clear that as long as cGMP remains inthe smooth muscle tissue, the muscle is unable to contract. Therelaxation of the smooth muscle in the corpus cavernosum allows blood toflow into the penis, where it becomes trapped. The degradation andsubsequent disappearance of cGMP from the smooth muscle tissue resultsin contraction and normal blood flow into and out of the corpuscavernosum. Therefore, cGMP is the final product of several steps neededto initiate, promote, and maintain a penile erection.

The cGMP produced in the smooth muscle tissue of the corpus cavernosumis broken down after a short time. But as long as sexual stimulationcontinues, the degraded cGMP is continuously replaced by more NO-inducedcGMP and erection continues. Cyclic nucleotide phosphodiesterases,specifically Type 5, break down cGMP to GMP by catalyzing a reactionthat breaks the phosphodiester bond using H₂O. Phosphodiesterase type 5(PDE5) thereby impedes the actions of cGMP in maintaining penileerection.

Multiple studies in dogs and humans have concluded that sildenafil worksby inhibiting PDE5, the enzyme responsible for the degradation of cGMP.Sildenafil, therefore, does not act directly on the corpus cavernosum,but enhances the nitric oxide-cGMP (i.e., NO-cGMP) pathway. Morespecifically, sildenafil affects the last step in the NO-cGMP pathway.Therefore, all the preceding steps must occur in order to have a penileerection. Sexual stimulation is the trigger to the whole NO-cGMP pathwayand this remains true of the pathway when sildenafil is used. Sildenafilhelps maintain high levels of cGMP in the corpus cavernosum bypreventing PDE5 from breaking it down. Sildenafil's inhibition of PDE5increases the length of time that cGMP remains in the smooth muscletissue, and therefore, increases chances of erection. At recommendeddoses, sildenafil has no effect without sexual stimulation. Vardenafilis anticipated to work in a similar manner and have similar results tosildenafil.

A recent study demonstrated that erectile responses result fromtreatment of penile tissue with vasodilator agents that elevate cyclicnucleotides in penile cavernosal smooth muscle, including vasoactiveintestinal polypeptide (VIP) and PGE₁, in addition to sildenafil. Thealpha-adrenergic receptor blocking agent phentolamine has beendemonstrated to potentiate the effects of vasodilator agents, presumablythrough its inhibition of sympathetic input to the penis.

As indicated above, the present invention is directed to systems andmethods for treating erectile dysfunction, such as erectile dysfunctionthat follows prostatic surgery. In accordance with the teachings of thepresent invention, electrical stimulation and/or one or more stimulatingdrugs are applied to one or more of the above mentioned areas as atreatment for such erectile dysfunction. As used herein, stimulate,stimulation, and stimulating refer to supplying electrical currentpulses and/or infusion of a stimulating drug(s). As such, electricalcurrent parameters and/or infusion parameters are sometimes referred toherein as simply stimulation parameters, which parameters may includeamplitude, volume, pulse width, infusion rate, and the like. Similarly,stimulation pulses may be pulses of electrical energy and/or pulses ofdrugs infused by various means and rates of infusion, such asintermittent infusion, infusion at a constant rate, and bolus infusion.

Herein, stimulating drugs comprise medications, anesthetic agents,synthetic or natural hormones, neurotransmitters, interleukins(including cytokines, lymphokines, chemokines, and growth factors),genes, gene products, and other intracellular and intercellular chemicalsignals and messengers, and the like. In addition, certainneurotransmitters, hormones, and other drugs are excitatory for sometissues, yet are inhibitory to other tissues. Therefore, where, herein,a drug is referred to as an “excitatory” drug, this means that the drugis acting in an excitatory manner, although it may act in an inhibitorymanner in other circumstances and/or locations. Similarly, where an“inhibitory” drug is mentioned, this drug is acting in an inhibitorymanner, although in other circumstances and/or locations, it may be an“excitatory” drug.

In some alternatives, an implantable signal generator and electrode(s)and/or an implantable pump and catheter(s) are used to deliverelectrical stimulation and/or one or more stimulating drugs to thetarget area(s). One or more electrodes are surgically implanted toprovide electrical stimulation, and/or one or more catheters aresurgically implanted to infuse the stimulating drug(s).

The invention includes at least one system control unit (SCU). In thecase of electrical stimulation only, an SCUs include an implantablepulse/signal generator (IPG), or the like. In the case of drug infusiononly, an SCU comprises an implantable pump or the like. In casesrequiring both electrical stimulation and drug infusion, more than oneSCU may be used. Alternatively, when needed and/or desired, an SCUprovides both electrical stimulation and one or more stimulating drugs.

In some embodiments, electrical and/or drug stimulation is provided byone or more system control units (SCUs) that are small, implantablestimulators, referred to herein as microstimulators. Themicrostimulators of the present invention may be similar to or of thetype referred to as BION® devices (see FIGS. 4A, 4B, and 4C). Thefollowing documents describe various details associated with themanufacture, operation and use of BION implantable microstimulators, andare all incorporated herein by reference:

Application/Patent/ Filing/Publication Publication No. Date Title U.S.Pat. No. 5,193,539 Issued Implantable Microstimulator Mar. 16, 1993 U.S.Pat. No. 5,193,540 Issued Structure and Method of Manufacture of anImplantable Mar. 16, 1993 Microstimulator U.S. Pat. No. 5,312,439 IssuedImplantable Device Having an Electrolytic Storage May 17, 1994 ElectrodeU.S. Pat. No. 5,324,316 Issued Implantable Microstimulator Jun. 28, 1994U.S. Pat. No. 5,405,367 Issued Structure and Method of Manufacture of anImplantable Apr. 11, 1995 Microstimulator PCT Publication PublishedBattery-Powered Patient Implantable Device WO 98/37926 Sep. 3, 1998 PCTPublication Published System of Implantable Devices For Monitoringand/or WO 98/43700 Oct. 8, 1998 Affecting Body Parameters PCTPublication Published System of Implantable Devices For Monitoringand/or WO 98/43701 Oct. 8, 1998 Affecting Body Parameters U.S. Pat. No.6,051,017 Issued Apr. 18, 2000 Improved Implantable Microstimulator andSystems (App. No. 09/077,662) (filed May 29, 1998) Employing SamePublished Micromodular Implants to Provide Electrical StimulationSeptember, 1997 of Paralyzed Muscles and Limbs, by Cameron, et al.,published in IEEE Transactions on Biomedical Engineering, Vol. 44, No.9, pages 781-790.

As shown in FIGS. 4A, 4B, and 4C, microstimulator SCUs 160 may include anarrow, elongated capsule 152 containing electronic circuitry 154connected to electrodes 172 and 172′, which may pass through the wallsof the capsule at either end. Alternatively, electrodes 172 and/or 172′may be built into the case and/or arranged on a catheter 180 (FIG. 4B)or at the distal portion of a lead, as described below. As detailed inthe referenced patents, electrodes 172 and 172′ generally comprise astimulating electrode (to be placed close to the target tissue) and anindifferent electrode (for completing the circuit). Other configurationsof microstimulator SCU 160 are possible, as is evident from theabove-referenced patent publications, and as described in more detailherein.

Certain configurations of SCU 160 are sufficiently small to permitplacement in or adjacent to the structures to be stimulated. Forinstance, in these configurations, capsule 152 may have a diameter ofabout 4-5 mm, or only about 3 mm, or even less than about 3 mm. In theseconfigurations, capsule length may be about 25-35 mm, or only about20-25 mm, or even less than about 20 mm. The shape of themicrostimulator may be determined by the structure of the desiredtarget, the surrounding area, and the method of implantation. A thin,elongated cylinder with electrodes at the ends, as shown in FIGS. 4A,4B, and 4C, is one possible configuration, but other shapes, such ascylinders, disks, spheres, and helical structures, are possible, as aredifferent configurations of and/or additional electrodes, infusionoutlets, leads, and/or catheters.

Microstimulator SCU 160, when certain configurations are used, may beimplanted with a surgical tool such as a tool specifically designed forthe purpose, or may be placed, for instance, via a small incision andthrough an insertion cannula. Alternatively, microstimulator SCU 160 maybe implanted via conventional surgical methods, or may be implantedusing other endoscopic or laparoscopic techniques. A more complicatedsurgical procedure may be required for sufficient access to a portion ofa nerve and/or for fixing the microstimulator in place.

The external surfaces of microstimulator SCU 160 may advantageously becomposed of biocompatible materials. Capsule 152 may be made of, forinstance, glass, ceramic or other material that provides a hermeticpackage that will exclude water vapor but permit passage ofelectromagnetic fields used to transmit data and/or power. Electrodes172 and 172′ may be made of a noble or refractory metal or compound,such as platinum, iridium, tantalum, titanium, titanium nitride,niobium, or alloys or any of these, in order to avoid corrosion orelectrolysis which could damage the surrounding tissues and the device.

In certain embodiments of the instant invention, microstimulator SCU 160comprises two, leadless electrodes. However, either or both electrodes172 and 172′ may alternatively be located at the distal portion ofshort, flexible leads as described in U.S. patent application Ser. No.09/624,130, filed Jul. 24, 2000, which is incorporated herein byreference in its entirety. The use of such leads permits, among otherthings, electrical stimulation to be directed more locally to targetedtissue(s) a short distance from the surgical fixation of the bulk ofmicrostimulator SCU 160, while allowing most elements of themicrostimulator to be located in a more surgically convenient site. Thisminimizes the distance traversed and the surgical planes crossed by thedevice and any lead(s). In most uses of this invention, the leads are nolonger than about 150 mm.

As seen in FIG. 5, some embodiments of SCU 160 may be (but are notnecessarily) implanted in a surgically-created shallow depression oropening, such as in the abdomen, pelvis, thorax, or above the buttock.In such embodiments, SCU 160 may conform to the profile of surroundingtissue(s) and/or bone(s), and is small and compact. This may minimizeupward pressure applied to the skin, which pressure may cause skinerosion or infection. Thus, in some embodiments, SCU 160 has a diameterof about 75 mm, or only about 65 mm, or even less than about 55 mm. Inthese configurations, SCU thickness may be approximately 10-12 mm, oreven less than about 10 mm.

As depicted in FIG. 5, in some embodiments, one or more electrode leads170 and/or catheters 180 attached to SCU 160 run subcutaneously, forinstance, in a surgically-created shallow groove(s) or channel(s) or ina fascial plane(s) to the tissue to be stimulated. Recessed placement ofthe SCU and the lead(s) and/or catheter(s) may decrease the likelihoodof erosion of overlying skin, and may minimize any cosmetic impact.

In embodiments such as in FIG. 5, electrode(s) 172 are carried on lead170 having a proximal portion coupled to SCU 160. The lead containswires electrically connecting electrodes 172 to SCU 160. SCU 160contains electrical components 154 that produce electrical stimulationpulses that travel through the wires of lead 170 and are delivered toelectrodes 172, and thus to the tissue surrounding electrodes 172. Toprotect the electrical components inside SCU 160, some or all of thecase of the SCU may be hermetically sealed. For additional protectionagainst, e.g., impact, the case may be made of metal (e.g. titanium) orceramic, which materials are also biocompatible. In addition, SCU 160may be configured to be Magnetic Resonance Imaging (MRI) compatible.

In the case of treatment alternatively or additionally constituting druginfusion, SCU 160 may contain at least one pump 162 for storing anddispensing one or more drugs through infusion outlet(s) 182 and/orcatheter(s) 180 into a predetermined site. When a catheter is used, itincludes at least one infusion outlet 182, usually positioned at leastat a distal end, and/or positioned at a distal portion of the catheter,while a proximal portion of the catheter is connected to SCU 160.

According to some embodiments of the invention, such as depicted in FIG.5, at least one lead 170 is attached to SCU 160, via a suitableconnector 168, if necessary. Each lead includes at least two electrodes172, and may include as many as sixteen or more electrodes 172,positioned at a distal portion of the lead (as used herein, “at a distalportion” includes at the tip or anywhere on the distal end or section ofthe lead). Additional leads 170′ and/or catheter(s) 180′ may be attachedto SCU 160. Hence, FIG. 5 shows (in phantom lines) a second catheter180′, and a second lead 170′, having electrodes 172′ thereon, alsoattached to SCU 160. Similarly, the SCUs 160 of FIGS. 4A, 4B, and 4Chave outlets 182, 182′ for infusing a stimulating drug(s) and electrodes172, 172′ for applying electrical stimulation.

Lead(s) 170/170′ of certain embodiments of the present invention may beless than about 5 mm in diameter, or even less than about 1.5 mm indiameter. Electrodes 172/172′ on leads 170/170′ may be arranged as anarray, for instance, as two or more collinear electrodes, or even asfour or more collinear electrodes, or they may not be collinear. A tipelectrode may also be supplied at the distal end of one or more leads.In some embodiments, SCU 160 is programmable to produce either monopolarelectrical stimulation, e.g., using the SCU case as an indifferentelectrode, or bipolar electrical stimulation, e.g., using one of theelectrodes of the electrode array as an indifferent electrode. Someembodiments of SCU 160 have at least four channels and drive up tosixteen electrodes or more.

SCU 160 (which herein refers to IPGs, implantable pumps, IPG/pumpcombinations, microstimulators for drug and/or electrical stimulation,other alternative devices described herein, and the like) contains, whennecessary and/or desired, electronic circuitry 154 for receiving dataand/or power from outside the body by inductive, radio frequency (RF),or other electromagnetic coupling. In some embodiments, electroniccircuitry 154 includes an inductive coil for receiving and transmittingRF data and/or power, an integrated circuit (IC) chip for decoding andstoring stimulation parameters and generating stimulation pulses (eitherintermittent or continuous), and additional discrete electroniccomponents required to complete the electronic circuit functions, e.g.capacitor(s), resistor(s), coil(s), and the like.

SCU 160 also includes, when necessary and/or desired, a programmablememory 164 for storing a set(s) of data, stimulation, and controlparameters. Among other things, memory 164 may allow electrical and/ordrug stimulation to be adjusted to settings that are safe andefficacious with minimal discomfort for each individual. Specificparameters may provide therapy for various types and degrees of erectiledysfunction. For instance, some patients may respond favorably tointermittent stimulation, while others may require continuous treatmentto treat their dysfunction. In some embodiments, electrical and drugstimulation parameters are controlled independently. In variousembodiments, they are coupled, e.g., electrical stimulation isprogrammed to occur only during drug infusion.

In addition, parameters may be chosen to target specific tissues and toexclude others. For example, parameters may be chosen to increase neuralactivity in specific neural populations and to decrease neural activityin others. As another example, relatively low frequency neurostimulation(i.e., less than about 50-100 Hz) typically has an excitatory effect onsurrounding neural tissue, leading to increased neural activity, whereasrelatively high frequency neurostimulation (i.e., greater than about50-100 Hz) may have an inhibitory effect, leading to decreased neuralactivity.

Similarly, excitatory neurotransmitters (e.g., acetylcholine), agoniststhereof, and agents that increase levels of an excitatoryneurotransmitter(s) (e.g., edrophonium) generally have an excitatoryeffect on neural tissue, while inhibitory neurotransmitters (e.g.,gamma-aminobutyric acid, a.k.a. GABA), agonists thereof, and agents thatact to increase levels of an inhibitory neurotransmitter(s) generallyhave an inhibitory effect. However, antagonists of inhibitoryneurotransmitters (e.g., bicuculline) and agents that act to decreaselevels of an inhibitory neurotransmitter(s) have been demonstrated toexcite neural tissue, leading to increased neural activity. Similarly,excitatory neurotransmitter antagonists (e.g., atropine, oxybutynin) andagents that decrease levels of excitatory neurotransmitters may inhibitneural activity.

Some embodiments of SCU 160 also include a power source and/or powerstorage device 166. Possible power options for a stimulation device ofthe present invention, described in more detail below, include but arenot limited to an external power source coupled to the stimulationdevice, e.g., via an RF link, a self-contained power source utilizingany means of generation or storage of energy (e.g., a primary battery, areplenishable or rechargeable battery such as a lithium ion battery, anelectrolytic capacitor, or a super- or ultra-capacitor), and if theself-contained power source is replenishable or rechargeable, means ofreplenishing or recharging the power source (e.g., an RF link, anoptical link, a thermal link, or other energy-coupling link).

In embodiments such as shown in FIG. 5, SCU 160 includes a rechargeablebattery as a power source/storage device 166. The battery is recharged,as required, from an external battery charging system (EBCS) 192,typically through an inductive link 194. In these embodiments, SCU 160includes a processor and other electronic circuitry 154 that allow it togenerate stimulation pulses that are applied to a patient 208 throughelectrodes 172 and/or outlet(s) 182 in accordance with a program andstimulation parameters stored in programmable memory 164. Stimulationpulses of drugs include various types and/or rates of infusion, such asintermittent infusion, infusion at a constant rate, and bolus infusion.

According to certain embodiments of the invention, an SCU operatesindependently. According to various embodiments of the invention, an SCUoperates in a coordinated manner with other SCU(s), other implanteddevice(s), or other device(s) external to the patient's body. Forinstance, an SCU may control or operate under the control of anotherimplanted SCU(s), other implanted device(s), or other device(s) externalto the patient's body. An SCU may communicate with other implanted SCUs,other implanted devices, and/or devices external to a patient's bodyvia, e.g., an RF link, an ultrasonic link, a thermal link, or an opticallink. Specifically, an SCU may communicate with an external remotecontrol (e.g., patient and/or physician programmer) that is capable ofsending commands and/or data to an SCU and that may also be capable ofreceiving commands and/or data from an SCU.

For example, some embodiments of SCU 160 of the present invention may beactivated and deactivated, programmed and tested through a hand heldprogrammer (HHP) 200 (which may also be referred to as a patientprogrammer and may be, but is not necessarily, hand held), a clinicianprogramming system (CPS) 202 (which may also be hand held), and/or amanufacturing and diagnostic system (MDS) 204 (which may also be handheld). HHP 200 may be coupled to SCU 160 via an RF link 195. Similarly,MDS 204 may be coupled to SCU 160 via another RF link 196. In a likemanner, CPS 202 may be coupled to HHP 200 via an infra-red link 197; andMDS 204 may be coupled to HHP 200 via another infra-red link 198. Othertypes of telecommunicative links, other than RF or infra-red may also beused for this purpose. Through these links, CPS 202, for example, may becoupled through HHP 200 to SCU 160 for programming or diagnosticpurposes. MDS 204 may also be coupled to SCU 160, either directlythrough the RF link 196, or indirectly through IR link 198, HHP 200, andRF link 195.

In certain embodiments, using for example, a microstimulator(s) asdescribed herein, and as illustrated in FIG. 6, the patient 208 switchesSCU 160 on and off by use of controller 210, which may be handheld.Controller 210 operates to control SCU 160 by any of various means,including sensing the proximity of a permanent magnet located incontroller 210, sensing RF transmissions from controller 210, or thelike. Other means of controlling SCU are possible, such as an implantedbutton that may be pressed to activate SCU 160.

External components of various embodiments for programming and providingpower to SCU 160 are also illustrated in FIG. 6. When it is required tocommunicate with SCU 160, patient 208 is positioned on or near externalappliance 220, which appliance contains one or more inductive coils 222or other means of communication (e.g., RF transmitter and receiver).External appliance 220 is connected to or is a part of externalelectronic circuitry appliance 230 which may receive power 232 from aconventional power source. External appliance 230 contains manual inputmeans 238, e.g., a keypad, whereby the patient 208 or a caregiver 242may request changes in electrical and/or drug stimulation parametersproduced during the normal operation of SCU 160. In these embodiments,manual input means 238 include various electromechanical switches and/orvisual display devices that provide the patient and/or caregiver withinformation about the status and prior programming of SCU 160.

Alternatively or additionally, external electronic appliance 230 isprovided with an electronic interface means 246 for interacting withother computing means 248, such as by a serial interface cable orinfrared link to a personal computer, to a telephone modem, or the like.Such interface means 246 may permit a clinician to monitor the status ofthe implant and prescribe new stimulation parameters from a remotelocation.

The external appliance(s) may be embedded in a cushion, pillow, mattresscover, or garment. Other possibilities exist, including a belt, patch,or other structure(s) that may be affixed to the patient's body orclothing. External appliances may include a package that can be, e.g.,worn on the belt, may include an extension to a transmission coilaffixed to the body, e.g., with a velcro band or adhesive, or may becombinations of these or other structures able to perform the functionsdescribed herein.

To help determine the strength and/or duration of electrical stimulationand/or the amount and/or type(s) of stimulating drug(s) required toproduce the desired effect, in some embodiments, a patient's response toand/or need for treatment is sensed. For example, changes in penilearteriole pressure produced in response to stimulation may be sensed.Other measures of the state of the patient may additionally oralternatively be sensed, e.g., pressure in corpus cavernosum, pressurein corpus spongiosum, joint angle, tumescence, muscle activity (e.g.,EMG), nerve activity (e.g., ENG, cavernous nerve firing rate),electrical activity of the brain (e.g., EEG), neurotransmitter levelsand/or their associated breakdown product levels, hormone levels,interleukin levels, or other substances, such as ketone, electrolyte,enzyme, and/or medication levels, and/or changes in these or othersubstances in the blood plasma or local interstitial fluid, may besensed. Substances may be sensed, for instance, using one or moreChemically Sensitive Field-Effect Transistors (CHEMFETs) such asEnzyme-Selective Field-Effect Transistors (ENFETs) or Ion-SensitiveField-Effect Transistors (ISFETs, as are available from Sentron CMT ofEnschede, The Netherlands).

For example, when electrodes and/or catheters of SCU 160 are implantedadjacent to greater cavernous nerve 108, signals from a pressure sensorbuilt into SCU 160 may be recorded. (As used herein, “adjacent” and“near” mean as close as reasonably possible to targeted tissue,including touching, being attached to, or even being positioned withinthe tissue, but in general, may be as far as about 150 mm from thetarget tissue. In addition, as used herein, “tissue affecting the penis”includes tissue of the penis itself.)

Alternatively, an “SCU” dedicated to sensory processes communicates withan SCU that provides the stimulation pulses. The implant circuitry 154may, if necessary, amplify and transmit these sensed signals, which maybe digital or analog. Other methods of determining the requiredelectrical and/or drug stimulation include observing the stimulationrequired to initiate and maintain erection, as well as other methodsmentioned herein, and others that will be evident to those of skill inthe art upon review of the present disclosure. The sensed informationmay be used to control stimulation parameters in a closed-loop manner.

For instance, in several embodiments of the present invention, a firstand second “SCU” are provided. The second “SCU” periodically (e.g., onceper minute) records a level of muscle activity (or neural activity,etc.), which it transmits to the first SCU. The first SCU uses thesensed information to adjust electrical and/or drug stimulationparameters according to an algorithm programmed, e.g., by a physician.For example, the amplitude of electrical stimulation may be increased inresponse to decreased penile arteriole pressure. In some alternatives,one SCU performs both the sensing and stimulating functions, asdiscussed in more detail presently.

While an SCU 160 may also incorporate means of sensing dysfunction, itmay alternatively or additionally be desirable to use a separate orspecialized implantable device to record and telemeter physiologicalconditions/responses in order to adjust electrical stimulation and/ordrug infusion parameters. This information may be transmitted to anexternal device, such as external appliance 220, or may be transmitteddirectly to implanted SCU(s) 160. However, in some cases, it may not benecessary or desired to include a sensing function or device, in whichcase stimulation parameters are determined and refined, for instance, bypatient feedback, or the like.

Thus, it is seen that in accordance with the present invention, one ormore external appliances may be provided to interact with SCU 160, andmay be used to accomplish, potentially among other things, one or moreof the following functions:

-   -   Function 1: If necessary, transmit electrical power from the        external electronic appliance 230 via appliance 220 to SCU 160        in order to power the device and/or recharge the power        source/storage device 166. External electronic appliance 230 may        include an automatic algorithm that adjusts electrical and/or        drug stimulation parameters automatically whenever the SCU(s)        160 is/are recharged.    -   Function 2: Transmit data from the external appliance 230 via        the external appliance 220 to SCU 160 in order to change the        parameters of electrical and/or drug stimulation produced by SCU        160.    -   Function 3: Transmit sensed data indicating a need for treatment        or in response to stimulation from SCU 160 (e.g., impedance,        pressure, joint angle, electromyographical activity, level of a        blood-borne substance(s), or other activity) to external        appliance 230 via external appliance 220.    -   Function 4: Transmit data indicating state of the SCU 160 (e.g.,        battery level, drug level, stimulation parameters, etc.) to        external appliance 230 via external appliance 220.

By way of example, a treatment modality for erectile dysfunction may becarried out according to the following sequence of procedures:

-   -   1. An SCU 160 is implanted so that at least one infusion outlet        182 is adjacent to greater cavernous nerve 108 and/or a blood        vessel(s) supplying the penis (e.g., left and/or right deep        artery of the penis). If necessary or desired, electrodes 172,        172′ and/or additional infusion outlet(s) 182′ may be implanted        adjacent cavernous nerve 108 and/or other nerve fibers, blood        vessels, or other tissue, such as the lesser cavernous nerve        112, corpus cavernosum 116, and/or corpus spongiosum 128.    -   2. Using Function 2 described above (i.e., transmitting data) of        external electronic appliance 230 and external appliance 220,        SCU 160 is commanded to infuse a parasympathetic agonist, e.g.,        acetylcholine, and/or nitric oxide or an agonist thereof,        possibly in gradually increasing amounts, and possibly while        producing a series of excitatory electrical stimulation pulses,        possibly with gradually increasing amplitude. Alternatively, SCU        160 may be commanded to produce a series of excitatory        electrical stimulation pulses, possibly with gradually        increasing amplitude, and possible while infusing a        parasympathetic agonist and/or nitric oxide or an agonist        thereof, possibly in gradually increasing amounts.    -   3. After each stimulating infusion pulse, series of pulses, or        at some other predefined interval, any change in arteriole        pressure in arteries supplying the penis (and/or        intra-cavernosal pressure) resulting from the stimulation is        sensed, for instance, by one or more electrodes 172 and/or 172′        or sensors. These responses are converted to data and        telemetered out to external electronic appliance 230 via        Function 3.    -   4. From the response data received at external appliance 230        from SCU 160, the stimulus threshold for obtaining a response is        determined and is used by a clinician 242 acting directly 238 or        by other computing means 248 to transmit the desired drug and/or        electrical stimulation parameters to SCU 160 in accordance with        Function 2.    -   5. When patient 208 desires to invoke electrical stimulation        and/or drug infusion to instigate erection, he employs        controller 210 to set SCU 160 in a state where it delivers a        prescribed stimulation pattern from a predetermined range of        allowable stimulation patterns.    -   6. To allow his penis to return to a flaccid state, patient 208        employs controller 210 to turn off SCU 160.    -   7. Periodically, the patient or caregiver recharges the power        source/storage device 166 of SCU 160, if necessary, in        accordance with Function 1 described above (i.e., transmit        electrical power).

For the treatment of any of the various types and degrees of erectiledysfunction, it may be desirable to modify or adjust the algorithmicfunctions performed by the implanted and/or external components, as wellas the surgical approaches, in ways that would be obvious to skilledpractitioners of these arts. For example, in some situations, it may bedesirable to employ more than one SCU 160, each of which could beseparately controlled by means of a digital address. Multiple channelsand/or multiple patterns of electrical and/or drug stimulation mightthereby be programmed by the clinician and controlled by the patient inorder to deal with complex dysfunctions such as severe erectiledysfunction that requires stimulation of multiple nerves, e.g.,bilateral greater and lesser cavernous nerves, or for multipledysfunctions e.g., erectile dysfunction and incontinence.

In some embodiments discussed earlier, SCU 160, or a group of two ormore SCUs, is controlled via closed-loop operation. A need for and/orresponse to stimulation is sensed via SCU 160, or by an additional SCU(which may or may not be dedicated to the sensing function), or byanother implanted or external device. If necessary, the sensedinformation is transmitted to SCU 160. In some embodiments, thestimulation parameters used by SCU 160 are automatically adjusted basedon the sensed information. Thus, the electrical and/or drug stimulationparameters may be adjusted in a closed-loop manner to providestimulation tailored to the need for and/or response to the electricaland/or drug stimulation.

For instance, as shown in the example of FIG. 7, a first SCU 160,implanted beneath the skin of the patient 208, provides a firstmedication or substance; a second SCU 160′ provides a second medicationor substance; and a third SCU 160″ provides electrical stimulation viaelectrodes 172 and 172′. As mentioned earlier, the implanted devices mayoperate independently or may operate in a coordinated manner with othersimilar implanted devices, other implanted devices, or other devicesexternal to the patient's body, as shown by the control lines 262, 263and 264 in FIG. 7. That is, in accordance with certain embodiments ofthe invention, the external controller 250 controls the operation ofeach of the implanted devices 160, 160′ and 160″. According to variousembodiments of the invention, an implanted device, e.g. SCU 160, maycontrol or operate under the control of another implanted device(s),e.g. SCU 160′ and/or SCU 160″. That is, a device made in accordance withthe invention may communicate with other implanted stimulators, otherimplanted devices, and/or devices external to a patient's body, e.g.,via an RF link, an ultrasonic link, an optical link, or the like.Specifically, as illustrated in FIG. 7, SCU 160, 160′, and/or 160″, madein accordance with the invention, may communicate with an externalremote control (e.g., patient and/or physician programmer 250) that iscapable of sending commands and/or data to implanted devices and thatmay also be capable of receiving commands and/or data from implanteddevices.

A drug infusion stimulator made in accordance with the invention mayincorporate communication means for communicating with one or moreexternal or site-specific drug delivery devices, and, further, may havethe control flexibility to synchronize and control the duration of drugdelivery. The associated drug delivery device typically provides afeedback signal that lets the control device know it has received andunderstood commands. The communication signal between the implantedstimulator and the drug delivery device may be encoded to prevent theaccidental or inadvertent delivery of drugs by other signals.

An SCU made in accordance with some embodiments of the invention thusincorporates first sensing means 268 for sensing therapeutic effects,clinical variables, or other indicators of the state of the patient,such as ENG, EMG, EEG, pressure, joint angle, tumescence, impedance, orthe like. The stimulator additionally or alternatively incorporatessecond means 269 (e.g., a CHEMFET) for sensing neurotransmitter levelsand/or their associated breakdown product levels, medication levelsand/or other drug levels, hormone, ketone, electrolytes, enzyme, and/orinterleukin levels and/or changes in these or other substances in theblood plasma or local interstitial fluid. The stimulator additionally oralternatively incorporates third means 270 for sensing electricalcurrent levels and/or waveforms supplied by another source of electricalenergy. Sensed information may be used to control infusion and/orelectrical parameters in a closed loop manner, as shown by control lines266, 267, and 265. Thus, sensing means may be incorporated into a devicethat also includes electrical and/or drug stimulation, or the sensingmeans (that may or may not have stimulating means) may communicate thesensed information to another device(s) with stimulating means.

As indicated above, during nerve-sparing prostate surgery, the cavernousnerves are typically visualized and may be stimulated acutely forimproved localization and identification. During the procedure, if thecavernous nerves are identified, then according to certain embodimentsof the present invention, a means of stimulation, such as electrodes172/172′ are placed adjacent to one or more cavernous nerves and/oradjacent (such as within) other tissue(s) or blood vessel(s). In variousembodiments, when such nerves are identified, infusion outlet(s)182/182′ of catheter(s) 180/180′ are placed adjacent to one or bothcavernous nerves 108/112 or adjacent the corpus cavernosum 116 and/orother tissue(s) or blood vessel(s) to infuse stimulating dosages of oneor more drugs. The lead(s) 170/170′ and/or catheter(s) 180/180′ exit thepatient through the surgical entry site or another site created forexit, thus providing stimulation of the cavernous nerve(s) 108/112and/or other site(s).

Following surgery, the patient may regain normal erectile function.Therefore, the lead(s)/catheter(s) may be designed for easy removal withminimal or no surgical intervention. For instance, in-line lead(s) maybe used, which may simply be pulled out, or the lead(s)/catheter(s) mayhave a barb(s), which can be broken or overcome with minimal force.Alternatively, the proximal portion of the lead(s)/catheter(s) may beplaced in a subcutaneous pocket under the skin and left in place, or theproximal portion may be severed and the exit site closed over theremaining portion of the lead.

If the patient does not regain normal erectile function followingsurgery, then according to the teachings of the present invention, thepatient undergoes testing to determine if stimulation produces erection.Such testing may include connecting the proximal portion of thelead(s)/catheter(s) to an external stimulator which provides stimulationpulses through the electrode(s) and/or infusion outlet(s) in order toassess patient response to such stimulation. If erection is achievedwith stimulation, then the patient may elect to have the proximalportion of the lead(s)/catheter(s) attached to SCU 160, which is thenimplanted in the patient. In such cases, treatment is carried out asdescribed earlier, with lead(s) 170/170′ and/or catheter(s) 180/180′coupled at a proximal portion to SCU 160 and having electrode portion(s)172/172′ and/or catheter infusion outlet(s) 182/182′ providingstimulation to one or more of the cavernous nerves 108/112, corpuscavernosum 116, and/or other tissue(s) or blood vessel(s).

As a therapeutic alternative, electrode portion(s) 172/172′ and/orinfusion outlet(s) 182/182′ may additionally or alternatively beimplanted adjacent any structure or space of the penis, such as corpuscavernosa 116, corpus spongiosum 128, and/or parasympathetic targetsdeeper in the patient's body, such as one or more of the proximalportion of cavernous nerves 108 and 112, the prostatic plexus 107, thepelvic splanchnic nerves 100, and the second, third, and fourth sacralnerves S2, S3, S4. Electrodes 172/172′ and/or infusion outlet(s)182/182′ may also or instead be implanted adjacent to one or more of thehypogastric nerves 178, certain nerves of the inferior hypogastricplexus 104 or its branches, or the sympathetic ganglia from which theyarise, in order to inhibit sympathetic input that retards erection.Infusion outlet(s) 182/182′ and/or electrodes 172/172′ may also orinstead be implanted adjacent (e.g., within) any blood vessel supplyingor draining the penis, including the left and right internal iliacarteries 144, the left and right internal pudendal arteries 148, theleft and right dorsal arteries of the penis 142, the left and right deeparteries of the penis 140, the deep dorsal vein 150 of the penis, andthe urethra.

As yet another therapeutic alternative, one or more microstimulator SCUssuch as described earlier may be implanted to apply electrical and/ordrug stimulation to any of the above named structures. Themicrostimulator SCU(s) may be implanted at any time, such as duringprostate surgery. If not needed or desired after surgery, themicrostimulator(s) may remain implanted, or may be explanted.Alternatively, microstimulator SCUs may be implanted after prostatesurgery, or at any other time, to address erectile dysfunction.

According to certain embodiments, the patient is treated with increasedexcitement of the parasympathetic input to the penis. Relativelylow-frequency electrical stimulation (e.g., less than about 50-100 Hz)is likely to produce such excitement. Additionally or alternatively,substances that may be infused to promote erection includeneurotransmitters and medications that act to increase parasympatheticactivation, such as acetylcholine and its agonists (i.e., cholinergicmedications), androgens (e.g., testosterone), alpha-adrenergicantagonists (e.g., phentolamine), prostaglandins (e.g., prostaglandinE₁, a.k.a. alprostadil), and vasodilators (e.g., papaverine).

According to various embodiments, the patient is treated by inhibitingexcitement of sympathetic input to the penis. In this case, relativelyhigh-frequency electrical stimulation (e.g., greater than about 50-100Hz) is likely to produce such inhibition. Substances that may also orinstead be used to decrease sympathetic activation includeneurotransmitters and medications such as GABA, an inhibitoryneurotransmitter, and/or norepinephrine antagonists (i.e.,adrenergic-blocking medications) such as the alpha-adrenergic receptorblocking agent phentolamine.

Additional or alternative substances that may be infused to any of theabove-named nerves, tissues, and/or blood vessels include vasodilatoragents that elevate cyclic nucleotides in penile cavernosal smoothmuscle, including vasoactive intestinal polypeptide (VIP) and PGE₁, aswell as sildenafil, vardenafil, and/or other agent(s) that inhibitPhosphodiesterase type 5 (PDE5) or otherwise inhibit degradation ofguanosine 3′,5′-cyclic monophosphate (a.k.a., cyclic GMP or cGMP).Substances may also or instead include other substances known to resultin an erectile response, such as one or more of acetylcholine, nitricoxide (NO), analogs of nitric oxide, guanylyl cyclase NO receptoragonists, and cGMP. Therapeutic substances may include traditionalagents used in intracavernosal injection therapy or other therapy forerectile dysfunction, including alprostadil, papaverine, phentolamine,and androgens, such as testosterone and dihydrotestosterone (DHT).Therapeutic substances may also include genes or gene products that leadto an improvement in erectile response.

For example, SCU 160 may contain an infusion pump that releases NO usingmaterials that slowly release NO gas, such as recently developedpolymers containing derivatized silica particles that slowly release NOgas. In such embodiments, the infusion pump may draw interstitial fluidfrom surrounding tissue or from a source catheter or inlet, and when SCU160 is activated to produce an erection, it runs this interstitial fluidover a surface that releases NO and delivers the fluid containing NO to,for instance, one or both corpus cavernosa 116, via a deliverycatheter/infusion outlet. In such embodiments, a source catheter/inletand a delivery catheter/outlet may be the same or different.Additionally, SCU 160 may have a fluid (e.g., saline) reservoir, and thefluid from this reservoir may be passed over the surface that releasesNO and to the stimulation target. The surface that releases NO may be apart of the delivery catheter/infusion outlet, or these items may beseparate.

In yet another alternative, placement of electrodes 172/172′ and/orinfusion outlet(s) 182/182′ may be chosen to effect emission (dischargeof semen) or ejaculation (ejection of semen in orgasm). Whileparasympathetic input is responsible for erection, sympathetic impulsesare required for ejaculation. As stated earlier, the sympathetic nervoussystem originates in the thoracic and lumbar regions of the spinal cord.It is believed that a portion of the sympathetic outflow leaving thespinal cord at the first and second lumbar segments travels through thelower lumbar or pelvic parts of the sympathetic trunk, then via theinferior hypogastric plexus, to arrive at the vas deferens, the seminalvesicles, and the prostate. Therefore, stimulating certain branches ofthe inferior hypogastric plexus that innervate the prostate, seminalvesicles, and vas deferens may lead to emission and/or ejaculation.Alternatively or additionally, stimulation of the pelvic splanchnicnerves leading to the prostate may cause emission and/or ejaculation.

Furthermore, sensing means described earlier may be used to orchestratefirst the stimulation of nerves that cause erection, and then, whenappropriate, the stimulation of nerves that cause ejaculation.Alternatively, this orchestration may be programmed, and not based on asensed condition.

While the invention herein disclosed has been described by means ofspecific embodiments and applications thereof, numerous modificationsand variations could be made thereto by those skilled in the art withoutdeparting from the scope of the invention set forth in the claims. Forinstance, the methods and systems described herein may benefit patientswho have not undergone prostatic surgery. In such cases, the electrodeportion and/or infusion outlet of any leads/catheters and/ormicrostimulator SCU(s) would be implanted in one or more of the areasdescribed above. If desired, the response to stimulation may bedetermined prior to full implantation of the system, as described above.In anther alternative, patients may choose to keep SCU external, withlead(s) and/or catheter(s) providing stimulation percutaneously.

1. A method for performing prostate surgery, comprising: during aprostate surgery: positioning an implantable device to stimulate atissue affecting the penis of the prostate surgery patient; stimulatingthe tissue affecting the penis of the prostate surgery patient, whereinstimulating the tissue affecting the penis of the prostate surgerypatient includes stimulating via at least one of electrical stimulationand drug infusion; and determining if the patient is responsive to thestimulation to promote erection.
 2. The method of claim 1 wherein: theimplantable device comprises a system control unit and at least one of alead and a catheter, wherein the lead includes at least one stimulatingelectrode at a distal portion of the lead and the catheter includes atleast one infusion outlet at a distal portion of the catheter and thesystem control unit is operably connected at least one system controlunit to a proximal portion of the at least one of the lead and thecatheter for the patient; providing operating power to the at least onesystem control unit; stimulating the tissue affecting the peniscomprises: providing stimulation parameters to the at least one systemcontrol unit; generating stimulation pulses in accordance with thestimulation parameters; and delivering the stimulation pulses via atleast one of the lead and the catheter to the tissue affecting thepenis.
 3. The method of claim 2 wherein the stimulation pulses areinfusion pulses providing at least one of an excitatory drug,acetylcholine, and an acetylcholine agonist.
 4. The method of claim 2wherein the stimulation pulses are electrical pulses.
 5. The method ofclaim 2 wherein the tissue affecting the penis comprises one or more ofthe sympathetic ganglia from which the hypogastric nerves arise, thehypogastric nerves, the nerves of the inferior hypogastric plexus, andthe nerves of the branches of the inferior hypogastric plexus.
 6. Themethod of claim 5 wherein the stimulation pulses are infusion pulsesproviding at least one of an inhibitory drug, GABA, phentolamine, and anorepinephrine antagonist.
 7. The method of claim 5 wherein thestimulation pulses are electrical pulses.
 8. The method of claim 1wherein the tissue affecting the penis supplies parasympathetic inputthat promotes erection and wherein the tissue affecting the peniscomprises at least one nerve of the cavernous nerves, the prostaticplexus, branches of the prostatic plexus, the pelvic splanchnic nerves,and the second, third, and fourth sacral nerves.
 9. The method of claim2 wherein stimulating the tissue affecting the penis comprises affectingemission or ejaculation.
 10. The method of claim 9 wherein the tissueaffecting the penis comprises at least one nerve of the branches of theinferior hypogastric plexus that innervate at least one of the prostate,seminal vesicles, and vas deferens.
 11. The method of claim 9 whereinthe at least one nerve comprises at least one of the pelvic splanchnicnerves leading to the prostate.
 12. The method of claim 2 furthercomprising: sensing a condition of the patient with at least one sensor;and using the sensed condition to adjust at least one of the stimulationparameters of the system control unit.
 13. A method for treating aprostatic surgery patient, comprising: providing a system control unitfor delivering stimulation to tissue; implanting the system control unitadjacent to tissue affecting the penis, so that the system control unitis generally within 150 mm of the tissue affecting the penis; applyingstimulation via the system control unit to determine if a patient witherectile dysfunction is responsive to stimulation to promote erection;providing operating power to the system control unit; providingstimulation parameters to the system control unit; generatingstimulation pulses in accordance with the stimulation parameters; anddelivering the stimulation pulses to the tissue affecting the penis. 14.The method of claim 13 wherein the system control unit is leadless. 15.The method of claim 13 wherein the system control unit includes at leastone of a lead and a catheter.
 16. A system comprising: an implantablestimulator comprising an implantable package housing electricalcircuitry configured to control localized application of at least one ofelectrical stimulation and chemical stimulation to a tissue affectingthe penis; a sensing device configured to sense a physiologicalcondition indicative of an erection of the penis: and a communicationlink between the electrical circuitry and the sensing device, whereinthe sensing device, the electrical circuitry, and the communication linkare in a closed loop to control one or more parameters of theapplication of the at least one of the electrical stimulation and thechemical stimulation.
 17. The system of claim 16, wherein at least partof the sensing device is housed in the implantable package.
 18. Thesystem of claim 16, wherein the sensing device comprises a pressuresensor.
 19. The system of claim 16, wherein the communication linkbetween the electrical circuitry and the sensing device is direct.